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Background and purpose: The aim of this study was to define the prevalence and characteristics of peri‐electrode edema in a prospective cohort of patients undergoing deep brain stimulation (DBS) surgery and to correlate it with clinical findings. Methods: We performed brain magnetic resonance imaging (MRI) between 7 and 20 days after surgery in 19 consecutive patients undergoing DBS surgery for Parkinson's disease. The T2‐weighted hyperintensity surrounding DBS leads was characterized and quantified. Any evidence of bleeding around the leads was also evaluated. Clinical and follow‐up data were recorded. In a subgroup of patients, a follow‐up MRI was performed 3–6 weeks after surgery. We also retrospectively reviewed the post‐operative computed tomography scans of patients who underwent DBS at our center since 2013. Results: Magnetic resonance imaging showed a peri‐lead edematous reaction in all (100%) patients, which was unilateral in three patients (15.8%). In six patients (31.6%), we detected minor peri‐lead hemorrhage. Edema completely resolved in eight out of 11 patients with a follow‐up MRI and was markedly reduced in the others. Most patients were asymptomatic but six (31.6%) manifested various degrees of confusional state without motor symptoms. We found no significant correlation between edema volume, distribution and any clinical feature, including new post‐operative neurological symptoms. The retrospective computed tomography analysis showed that peri‐electrode hypodensity consistent with edema is absent at early post‐operative imaging but is common at scans performed >3 days after surgery. Conclusions: Peri‐electrode edema is a common, transient reaction to DBS lead placement and a convincing relation between edema and post‐operative clinical status is lacking. [ABSTRACT FROM AUTHOR]

Gait disturbance is a common and severe symptom of Parkinson's disease that severely impairs quality of life. Current treatments provide only partial benefits with wide variability in outcomes. Also, deep brain stimulation of the subthalamic nucleus (STN-DBS), a mainstay treatment for bradykinetic-rigid symptoms and parkinsonian tremor, is poorly effective on gait. We applied a novel DBS paradigm, adjusting the current amplitude linearly with respect to subthalamic beta power (adaptive DBS), in one parkinsonian patient with gait impairment and chronically stimulated with conventional DBS. We studied the kinematics of gait and gait initiation (anticipatory postural adjustments) as well as subthalamic beta oscillations with both conventional and adaptive DBS. With adaptive DBS, the patient showed a consistent and long-lasting improvement in walking while retaining benefits on other disease-related symptoms. We suggest that adaptive DBS can benefit gait in Parkinson's disease possibly by avoiding overstimulation and dysfunctional entrainment of the supraspinal locomotor network., Competing Interests: IUI is Newronika S.p.A. consultant. IUI is Adjunct Professor at the Department of Neurology, NYU Grossman School of Medicine. IUI and LB received research fundings (paid to the Institution) by Newronika S.p.A. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Isaias, Caffi, Borellini, Ampollini, Locatelli, Pezzoli, Mazzoni and Palmisano.)

Background/Objectives : High cognitive reserve (CR) has been shown to have beneficial effects on global cognition, cognitive decline, and risk of dementia in Parkinson's disease (PD). We evaluated the influence of CR on the long-term cognitive outcomes of patients with PD who underwent subthalamic nucleus deep brain stimulation (STN-DBS). Methods: Twenty-five patients with PD underwent neuropsychological screening using the Montreal Cognitive Assessment (MoCA) at baseline, 1 year, and 5 years after bilateral STN-DBS. CR was assessed using the Cognitive Reserve Index questionnaire. According to CR score, patients were assigned to two different groups (LowCR group ≤ 130, HighCR group > 130). Results: Our data showed that patients in the HighCR group obtained a better performance with the MoCA total score at long-term follow-up compared to those in the LowCR group ([mean ± SE] LowCR group: 21.4 ± 1.2 vs. HighCR group: 24.5 ± 1.3, p = 0.05). The cognitive profile of the HighCR group remained unchanged over time. Conversely, the LowCR group had worse global cognition 5 years after surgery (T0: 25.3 ± 0.6 vs. T2: 21.4 ± 1.2, p = 0.02). Cognitive decline was not associated with mood, demographics, or clinical variables. Conclusions: These preliminary findings suggest that higher CR may be protective in PD cognition after STN-DBS. Specifically, a high CR may help cope with long-term decline in the context of surgical treatment. Quantifying a patient's CR could lead to more personalized medical care, tailoring postoperative support and monitoring for those at higher risk of cognitive decline.

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Developmental and epileptic encephalopathy 45 (DEE45) is a neurogenetic disorder caused by heterozygous pathogenic variants of GABRB1, encoding the beta1 subunit of the GABA type A receptor. Only three infants with DEE45 have been reported so far, and a detailed description of the disease history of these patients is still lacking. We describe the clinical and genetic findings of a 21-year-old woman with DEE45 carrying a novel de novo GABRB1 mutation (c.841A>G, p.T281A). The patient presented at birth with hypotonia and focal apneic seizures evolving in a phenotype of epilepsy of infancy with migrating focal seizures that were refractory to antiseizure medications. Epileptic spasms partially responsive to steroid therapy appeared in the second year of life. Acquired microcephaly, profound mental retardation, and tetraparesis became evident with development. During childhood and adolescence, the epileptic phenotype evolved toward a Lennox-Gastaut Syndrome. Atypical absence status and clusters of tonic seizures occurred, often triggered by respiratory infections. The main strengths of this work are the identification of a novel pathogenic GABRB1 variant localized in the same transmembrane domain of a previously described mutation and the detailed description of the clinical trajectory of GABRB1-related encephalopathy along 21 years of disease history., (© 2023 The Authors. Epileptic Disorders published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objectives: Despite the large amount of literature examining the potential influence of subthalamic nucleus deep brain stimulation (STN-DBS) on psychiatric symptoms and cognitive disorders, only a few studies have focused on its effect on personality. We investigated the correlation between total electrical energy delivered (TEED) and the occurrence of depressive traits in patients with Parkinson disease (PD) after one year of DBS., Materials and Methods: Our study involved 20 patients with PD (12 women, mean [±SD] age 57.60 ± 7.63 years) who underwent bilateral STN-DBS, whose personality characteristics were assessed using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), according to the core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD) procedure., Results: We found that despite a marked improvement in motor functions and quality of life after 12 months, patients showed a significant increase in MMPI-2 subscales for depression (D scale and Depression scale) and in other content component scales (low self-esteem, work interference, and negative treatment indicators). Interestingly, only the TEED on the right side was inversely correlated with the changes in scale D (r s  = -0.681, p = 0.007), whereas depressive traits did not correlate with disease duration, levodopa equivalent daily dose (LEDD) reduction, patient's age, or severity of motor symptoms., Conclusions: Our preliminary observations indicate that despite the excellent motor outcome and general improvement in quality of life, DBS treatment can result in patients poorly adjusting to their personal, familiar, and socio-professional life. Different influences and multiple factors (such as TEED, intra/postsurgical procedure, coping mechanisms, and outcome expectations) may affect depressive traits. Further advances are expected to improve stimulation methods., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Diffusion tensor imaging (DTI) allows visualization of the main white matter tracts while intraoperative neurophysiological monitoring (IONM) represents the gold standard for surgical resection of gliomas. In recent years, the use of small craniotomies has gained popularity thanks to neuronavigation and to the low morbidity rates associated with shorter surgical procedures. The aim of this study was to review a series of patients operated for glioma using DTI, IONM, and tumor-targeted craniotomies. The retrospective analysis included patients with supratentorial glioma who met the following inclusion criteria: preoperative DTI, intraoperative IONM, tumor-targeted craniotomy, pre- and postoperative MRI, and complete clinical charts. The DTI was performed on a 3T scanner. The IONM included electroencephalography (EEG), transcranial (TC) and/or cortical motor-evoked potentials (MEP), electrocorticography (ECoG), and direct electrical stimulation (DES). Outcomes included postoperative neurological deficits, volumetric extent of resection (EOR), and overall survival (OS). One hundred and three patients (61 men, 42 women; mean age 54 ± 14 years) were included and presented the following WHO histologies: 65 grade IV, 19 grade III, and 19 grade II gliomas. After 3 months, only three patients had new neurological deficits. The median postoperative volume was 0cc (IQR 3). The median OS for grade IV gliomas was 15 months, while for low-grade gliomas it was not reached. In our experience, a small craniotomy and a tumor resection supported by IONM and DTI permitted to achieve satisfactory results in terms of neurological outcomes, EOR, and OS for glioma patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Carrabba, Fiore, Di Cristofori, Bana, Borellini, Zarino, Conte, Triulzi, Rocca, Giussani, Caroli, Locatelli and Bertani.)

Implanting deep brain stimulation (DBS) electrodes in patients with Parkinson's disease often results in the appearance of a non-infectious, delayed-onset edema that disappears over time. However, the time window between the DBS electrode and DBS stimulating device implant is often used to record local field potentials (LFPs) which are used both to better understand basal ganglia pathophysiology and to improve DBS therapy. In this work, we investigated whether the presence of post-surgery edema correlates with the quality of LFP recordings in eight patients with advanced Parkinson's disease implanted with subthalamic DBS electrodes. The magnetic resonance scans of the brain after 8.5 ± 1.5 days from the implantation surgery were segmented and the peri-electrode edema volume was calculated for both brain hemispheres. We found a correlation ( ρ = -0.81, p < 0.0218, Spearman's correlation coefficient) between left side local field potentials of the low beta band (11-20 Hz) and the edema volume of the same side. No other significant differences between the hemispheres were found. Despite the limited sample size, our results suggest that the effect on LFPs may be related to the edema localization, thus indicating a mechanism involving brain networks instead of a simple change in the electrode-tissue interface., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Prenassi, Borellini, Bocci, Scola, Barbieri, Priori, Ferrucci, Cogiamanian, Locatelli, Rampini, Vergari, Pastore, Datola and Marceglia.)

Deep brain stimulation (DBS) is used for the treatment of movement disorders, including Parkinson's disease, dystonia, and essential tremor, and has shown clinical benefits in other brain disorders. A natural path for the improvement of this technique is to continuously observe the stimulation effects on patient symptoms and neurophysiological markers. This requires the evolution of conventional deep brain stimulators to bidirectional interfaces, able to record, process, store, and wirelessly communicate neural signals in a robust and reliable fashion. Here, we present the architecture, design, and first use of an implantable stimulation and sensing interface (AlphaDBS R System) characterized by artifact-free recording and distributed data management protocols. Its application in three patients with Parkinson's disease (clinical trial n. NCT04681534) is shown as a proof of functioning of a clinically viable implanted brain-computer interface (BCI) for adaptive DBS. Reliable artifact free-recordings, and chronic long-term data and neural signal management are in place., Competing Interests: MA and MC were employed by Newronika and held stock options. AB is a consultant for Newronika. AP, SM, and PR are founders and shareholders of Newronika. The study was funded by Newronika SpA. The funder had the following involvement with the study: study design of NCT04681534, signal collection and analysis (clinical data collection is performed by a CRO), the writing of this article, and the decision to submit it for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Arlotti, Colombo, Bonfanti, Mandat, Lanotte, Pirola, Borellini, Rampini, Eleopra, Rinaldo, Romito, Janssen, Priori and Marceglia.)

The progressive reduction of the dopaminergic neurons of the substantia nigra is the fundamental process underlying Parkinson's disease (PD), while the mechanism of susceptibility of this specific neuronal population is largely unclear. Disturbances in mitochondrial function have been recognized as one of the main pathways in sporadic PD since the finding of respiratory chain impairment in animal models of PD. Studies on genetic forms of PD have provided new insight on the role of mitochondrial bioenergetics, homeostasis, and autophagy. PINK1 (PTEN-induced putative kinase 1) gene mutations, although rare, are the second most common cause of recessively inherited early-onset PD, after Parkin gene mutations. Our knowledge of PINK1 and Parkin function has increased dramatically in the last years, with the discovery that a process called mitophagy, which plays a key role in the maintenance of mitochondrial health, is mediated by the PINK1/Parkin pathway. In vitro and in vivo models have been developed, supporting the role of PINK1 in synaptic transmission, particularly affecting dopaminergic neurons. It is of paramount importance to further define the role of PINK1 in mitophagy and mitochondrial homeostasis in PD pathogenesis in order to delineate novel therapeutic targets.

Introduction: Coronavirus disease 2019 (COVID-19) is associated to neuromuscular symptoms in up to 10.7% of hospitalized patients. Nevertheless, the extent of muscular involvement in infected subjects with no signs of myopathy has never been assessed with neurophysiological investigations., Methods: Over a 3-week period - from April 30 through May 20, 2020 - a total of 70 patients were hospitalized in the Internal Medicine Ward of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan, Italy. After excluding patients who underwent invasive ventilation and steroid treatment, 12 patients were evaluated. Nerve conduction studies (NCS) included the analysis of conduction velocity, amplitude, and latency for bilateral motor tibial, ulnar nerves, and sensory sural and radial nerves. Unilateral concentric-needle electromyography (EMG) was performed evaluating at least 4 areas of 8 selected muscles. For each muscle, spontaneous activity at rest, morphology, and recruitment of motor unit action potentials (MUAPs) were evaluated., Results: While nerve conduction studies were unremarkable, needle electromyography showed myopathic changes in 6 out of 12 subjects. All patients were asymptomatic for muscular involvement. Clinical features and laboratory findings did not show relevant differences between patients with and without myopathic changes., Conclusion: Our data show that in SARS-CoV-2 infection muscular involvement can occur despite the absence of clinical signs or symptoms and should be considered part of the disease spectrum. The application of muscle biopsy to unravel the mechanisms of myofiber damage on tissue specimens could help to clarify the pathogenesis and the treatment response of coronavirus-mediated injury., (© 2021. Fondazione Società Italiana di Neurologia.)

This study compares the effects on motor symptoms between conventional deep brain stimulation (cDBS) and closed-loop adaptive deep brain stimulation (aDBS) in patients with Parkinson's Disease. The aDBS stimulation is controlled by the power in the beta band (12-35 Hz) of local field potentials recorded directly by subthalamic nucleus electrodes. Eight subjects were assessed in two 8-h stimulation sessions (first day, cDBS; second day, aDBS) with regular levodopa intake and during normal daily activities. The Unified Parkinson's Disease Rating Scale (UPDRS) part III scores, the Rush scale for dyskinesias, and the total electrical energy delivered to the tissues per second (TEEDs) were significantly lower in the aDBS session (relative UPDRS mean, cDBS: 0.46 ± 0.05, aDBS: 0.33 ± 0.04, p = 0.015; UPDRS part III rigidity subset mean, cDBS: 2.9143 ± 0.6551 and aDBS: 2.1429 ± 0.5010, p = 0.034; UPDRS part III standard deviation cDBS: 2.95, aDBS: 2.68; p = 0.047; Rush scale, cDBS 2.79 ± 0.39 versus aDBS 1.57 ± 0.23, p = 0.037; cDBS TEEDs mean: 28.75 ± 3.36 µj s -1 , aDBS TEEDs mean: 16.47 ± 3.33, p = 0.032 Wilcoxon's sign rank test). This work further supports the safety and effectiveness of aDBS stimulation compared to cDBS in a daily session, both in terms of motor performance and TEED to the patient., (© 2021. The Author(s).)

Background: Adaptive Deep Brain Stimulation (aDBS) is now considered as a new feasible and effective paradigm to deliver DBS to patients with Parkinson's disease (PD) in such a way that not only stimulation is personalized and finely tuned to the instantaneous patient's state, but also motor improvement is obtained with a lower amount of energy transferred to the tissue. Amplitude-controlled aDBS was shown to significantly decrease the amplitude-driven total electrical energy delivered to the tissue (aTEED), an objective measure of the amount of energy transferred by DBS amplitude to the patient's brain. However, there is no direct evidence of a relationship between aTEED and the occurrence of DBS-related adverse events in humans. Objective: In this work, we investigated the correlation of aTEED with the occurrence of levodopa-induced dyskinesias pooling all the data available from our previous experiments using aDBS and cDBS. Methods: We retrospectively analyzed data coming from 19 patients with PD undergoing surgery for STN-DBS electrode positioning and participating to experiments involving cDBS and aDBS delivery. Patients were all studied some days after the surgery (acute setting). The aTEED and dyskinesia assessments (Rush Dyskinesia Rating Scale, RDRS) considered in the Med ON-Stim ON condition. Results: We confirmed both that aTEED values and RDRS were significantly lower in the aDBS than in cDBS sessions (aTEED mean value, cDBS: 0.0278 ± 0.0011 j, vs. aDBS: 0.0071 ± 0.0003 j, p < 0.0001 Wilcoxon's rank sum; normalized RDRS mean score, cDBS: 0.66 ± 0.017 vs. aDBS: 0.45 ± 0.01, p = 0.025, Wilcoxon's rank sum test). In addition, we found a direct significant correlation between aTEED and RDRS (ρ = 0.44, p = 0.0032, Spearman's correlation). Conclusions: Our results provide a first piece of evidence that aTEED is correlated to the amount of levodopa-induced dyskinesias in patients with PD undergoing STN-DBS, thus supporting the role of aDBS as feasible and safe alternative to cDBS., Competing Interests: SM, AP, SB, FC, PR, and ML are founder and shareholder of Newronika SpA, a spin-off company of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and of the University of Milan. MA was employed by the company Newronika SpA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Prenassi, Arlotti, Borellini, Bocci, Cogiamanian, Locatelli, Rampini, Barbieri, Priori and Marceglia.)

Background: For a long time, surgery of insular gliomas was considered at high risk for postoperative cognitive deficits, but recent studies highlighted the feasibility of the surgical approach. The aims of our study were to investigate the presence of language impairment before and after surgery and the relationship between language impairment and tumor volume preoperatively and extent of resection (EOR) 3 months after surgery., Methods: Thirty-five patients with insular gliomas underwent an extensive language assessment before and few days after surgery, and after 3 months. Intraoperative neurophysiological monitoring (IOM) and brain mapping with direct electrical stimulation (DES) were used in all the cases; 8 patients underwent awake craniotomy. Statistical analysis was performed on the language tests administered., Results: Patients with pure left insular lesion showed language impairment before and after surgery. Overall, patients with a left lesion showed a drop of performance after surgery followed by a partial recovery. Moreover, when the tumor involved the insula and adjacent networks, we observed a more severe deficit. No correlations were found between tumor volume, EOR, and language impairment., Conclusions: Left insular lobe is an important hub in language networks; its involvement determines pre- and postsurgical deficits, together with the involvement of white matter connections. Tumor volume and EOR are not risk factors per se directly related to language functioning. Surgery of insular gliomas is possible with a pre- and intraoperative extensive study of the patient with IOM and awake surgery, and encouraged by the trend of cognitive recovery highlighted.